- Email: [email protected]
Echocardiographic Evaluation of Systolic and Diastolic Function: A Preoperative Study of Correlation with Serum NT-proBNP
Echocardiographic Evaluation of Systolic and Diastolic Function: A Preoperative Study of Correlation with Serum NT-proBNP Christian Alcaraz Frederiksen, MD,*† Peter Juhl-Olsen, MD,*† Carl-Johan Jakobsen, MD,*† and Erik Sloth, MD, PhD, DMSc*† Objective: The authors hypothesized that preoperative Nterminal probrain natriuretic peptide (NT-proBNP) correlates well with longitudinal strain measurements and with Doppler measurements of diastolic function. Design: Prospective observational study. Setting: University teaching hospital. Participants: Forty patients undergoing elective cardiac surgery. Interventions: Aortic valve replacement, coronary artery bypass grafting, or a combination of these procedures. Measurements and Main Results: Plasma NT-proBNP concentration was obtained by analyzing blood samples with a commercially available kit. Left ventricular systolic function was assessed by speckle tracking ultrasound strain measurements and left ventricular diastolic function was assessed by 2 Doppler methods: E/A ratio and E/E= ratio. Tissue Doppler imaging velocities (E= and A=) were measured in the basal septum (annular) and pulse-wave Doppler was used to measure mitral in-flow profile (E and A). The correlation between global strain data from the speckle
tracking ultrasound measurement and NT-proBNP levels was ⴝ 0.35 (p ⴝ 0.026). With a cutoff value of ⴚ15% in global strain measurements, there was a significant difference in NT-proBNP levels (117 v 57 pg/mL, p ⴝ 0.048). E/E= values correlated with NT-proBNP levels ( ⴝ 0.46, p ⴝ 0.011). With a cutoff of 15 in E/E= values, there were significant differences in corresponding NT-proBNP levels (33 v 113 pg/mL, p ⴝ 0.004). Conclusions: A correlation was found between plasma levels of NT-proBNP and speckle tracking ultrasound strain measurements by an easily employed method applicable in the anesthesia and preoperative settings. In addition, the well-established marker of diastolic function, E/E=, correlated well with NT-proBNP, whereas the E/A ratio failed to show any association. © 2012 Elsevier Inc. All rights reserved.
T
of this study was to evaluate cardiac function by ultrasound imaging in combination with NT-proBNP before cardiac surgery. A secondary aim was to evaluate a simplified assessment of STU in the preoperative period using a single imaging plane and to assess its feasibility by comparison with a composite value from 3 imaging planes.
HE PREVALENCE OF systolic and diastolic heart failure is high and the prognosis is poor.1,2 Clinicians need information on hemodynamic performance and cardiovascular status in patients with a failing heart during cardiac and noncardiac surgery.3,4 Echocardiography is noninvasive and provides specific information about systolic and diastolic function, including important cardiac pathology.5 Systolic function can be assessed by measuring the degree of deformation in the myocardium by speckle tracking ultrasound (STU) strain measurements.6,7 A deformation analysis can be performed semiautomatically on 2-dimensional images acquired during conventional transthoracic echocardiography.8-10 Thus, physicians with limited training in echocardiography can generate measurements of myocardial deformation with a high degree of observer independency.10 Left ventricular (LV) diastolic function includes relaxation and filling of the chamber and advanced Doppler methods measuring blood flow velocities and tissue velocities are recommended for quantification.1 Overall assessment of cardiac function can be achieved by measuring serum N-terminal probrain natriuretic peptide (NTproBNP). Several studies have shown plasma levels of NTproBNP to be elevated in patients with systolic and diastolic heart failure11,12 and correlated to the prognosis in systolic heart failure.13 Similarly, studies have evaluated the use of NTproBNP levels as a prognostic tool during the perioperative period.14,15 The combination of cardiac biomarkers and ultrasound imaging may increase preoperative information on cardiac function, leading to increased safety during anesthesia and surgery. The authors hypothesized that preoperative NT-proBNP correlates well with longitudinal strain measurements and with Doppler measurements of diastolic function. The primary aim
KEY WORDS: echocardiography, preoperative, cardiac anesthesia, cardiac function, speckle tracking ultrasound, Doppler, strain, N-terminal probrain natriuretic peptide
METHODS Patients undergoing aortic valve replacement and/or coronary artery bypass grafting were included in the study that was performed in accordance with the Declaration of Helsinki and approved by the regional ethics committee (no M-ÅA-20050038). Written informed consent was obtained from all patients. Blood sampling and ultrasound examination were carried out the day before surgery. Plasma NT-proBNP concentration was determined with a commercially available kit (Roche Diagnostics, Mannheim, Germany). A Vivid E9 (GE Healthcare, Horten, Norway) ultrasound system equipped with an M5S-D phased array transducer (1.5 to 4.5 MHz) with second harmonic imaging was used for data acquisition. Examinations were performed with the patient in the left lateral position by a technician experienced in echocardiography. The protocol included imaging of the apical 4- and 2-chamber and long-axis views and the
From the *Department of Anesthesiology and Intensive Care, Aarhus University Hospital, and the †Institute of Clinical Medicine, Faculty of Health Sciences, Aarhus University, Skejby, Denmark. This work was funded by the John and Birthe Meyer Foundation. Address reprint requests to Christian Alcaraz Frederiksen, MD, Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Skejby, Brendstrupgaardsvej 100, DK-8200 Aarhus N, Denmark. E-mail: [email protected] © 2012 Elsevier Inc. All rights reserved. 1053-0770/2602-0004$36.00/0 doi:10.1053/j.jvca.2011.07.022
Journal of Cardiothoracic and Vascular Anesthesia, Vol 26, No 2 (April), 2012: pp 197-203
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Fig. 1. The 3 standard apical imaging planes and the corresponding bull’s eye plot. (Upper left) Apical 4-chamber view. (Upper right) Apical 2-chamber view. (Lower left) Apical long-axis view. (Lower right) Bull’s eye plot of the left ventricle showing myocardial strain in all segments. Strain data are based on calculations of measurements from all 3 apical imaging planes.
parasternal long- and short-axis views. Raw data were stored digitally in cineloop format defined by the R wave on the corresponding electrocardiogram for off-line analyses using EchoPac software (GE Healthcare). LV ejection fraction was calculated using the Simpson biplane method and LV deformation was assessed by STU based on the 3 standard imaging planes in the apical window. The method relies on natural acoustic markers in the tissue and is expressed as a percentage of change in tissue length during the cardiac cycle as the myocardial tissue shortens during contraction; longitudinal strain is expressed as negative values. The software processing is semiautomatic and based on manually placed regions of interest, including timing of the end of diastole and aortic valve closure. Deformation can be expressed as strain from a single imaging plane or as global strain calculated as the average value from the 3 apical imaging planes (Fig 1). Longitudinal, radial, or torsion strain measurements can be performed. All strain measurements in the present study were calculated as longitudinal strain. The cutoff value for STU strain measurements was ⫺15% in accordance with the age of the study population.16 Pulsed-wave Doppler was used for measuring mitral inflow blood velocities. The first peak in blood velocity early in diastole is designated E and the late or atrial peak in blood flow velocity is designated A. Tissue Doppler imaging of the septal mitral annulus was used for measuring tissue velocities throughout the cardiac cycle, with E= and A= corresponding to the above-mentioned mitral
inflow velocities. Two ratios related to LV diastolic function were calculated. The E/A ratio characterizes the filling pattern of the left ventricle. The E/E= ratio takes not only the blood flow but also the tissue movement into consideration and is related closely to LV filling pressures. Cutoff ratios between normal and abnormal values were 15 for E/E= and 0.9 for E/A.17-20 Comparisons of NT-proBNP and strain/Doppler values were based on the Spearman correlation and comparisons of NT-proBNP above and below the cutoff values were based on the Wilcoxon rank-sum test. STU data were compared according to the analyses of Bland and Altman.21,22 The level of statistical significance was p ⬍ 0.05. Tests and calculations were carried out using Stata 11.0 (StataCorp LP, College Station, TX). RESULTS
Forty patients were enrolled into the study. Basic clinical data and data on LV ejection fraction are presented in Tables 1, 2, and 3. Because of technical problems, E/E= and E/A measurements were available in only 29 subjects. No patient had a serum creatinine level ⬎200 mol/L preoperatively. A decrease in myocardial longitudinal strain correlated with an elevation in NT-proBNP levels. This applied when using global longitudinal strain data from all 3 imaging planes ( ⫽ 0.35, p ⫽ 0.026; Fig 2) and when using only STU data from the
ECHOCARDIOGRAPHIC SYSTOLIC AND DIASTOLIC FUNCTION
Table 1. N-Terminal Probrain Natriuretic Peptide and Clinical Characteristics Among Patients Undergoing Elective Cardiac Surgery Divided by Strain Above and Below ⴚ15%
NT-proBNP (pg/mL)* Age (y) BMI (kg/m2)* EF (%) Atrial fibrillation (n) Sex ⫽ male (%) CABG (n) AVR (n) CABG ⫹ AVR (n) EuroSCORE
STU Strain ⬎⫺15%
STU Strain ⱕ⫺15%
117 (66-168) 70 (68-73) 28 (27-30) 48 (42-55) 0 70 8 5 7 5.2 (4.2-6.1)
57 (32-81) 72 (70-74) 25 (23-26) 51 (47-56) 2 50 5 11 4 5.5 (4.7-6.3)
Abbreviations: AVR, aortic valve replacement; BMI, body mass index; CABG, coronary artery bypass grafting; EF, ejection fraction; NT-proBNP, N-terminal probrain natriuretic peptide; STU, speckle tracking ultrasound. *Significant differences.
199
Table 3. N-Terminal Probrain Natriuretic Peptide and Clinical Characteristics Among Patients Undergoing Elective Cardiac Surgery Divided by an E/A Ratio Above and Below 0.9
NT-proBNP (pg/mL) Age (y) BMI (kg/m2) EF (%) Atrial fibrillation (n) Sex ⫽ male (%) CABG (n) AVR (n) CABG ⫹ AVR (n) EuroSCORE
E/A ⱕ0.9
E/A ⬎0.9
89 (32-146) 70 (68-73) 27 (25-29) 52 (45-58) 0 55 5 4 2 5.3 (4.2-6.3)
70 (19-122) 72 (69-74) 26 (24-28) 50 (44-56) 2 61 6 7 5 5.0 (4.1-5.9)
Abbreviations: AVR, aortic valve replacement; BMI, body mass index; CABG, coronary artery bypass grafting; EF, ejection fraction; NT-proBNP, N-terminal probrain natriuretic peptide.
DISCUSSION
apical 4-chamber view ( ⫽ 0.43, p ⫽ 0.007; Fig 3). Furthermore, applying a cutoff value of ⫺15% to global strain measurements yielded a significant difference in NT-proBNP levels between patients with low (117 pg/mL) and high (57 pg/mL) global strain (p ⫽ 0.048). Global longitudinal strain and longitudinal strain from the apical 4-chamber view were compared using Bland-Altman analysis and showed a good agreement (p ⫽ 0.34; Figs 4 and 5). A decrease in diastolic function measured by an increase in E/E= correlated with an elevation in NT-proBNP levels ( ⫽ 0.46, p ⫽ 0.011; Fig 6). When a cutoff value of 15 was applied to E/E= values, there was a significant difference in corresponding NT-proBNP levels (33 v 113 pg/mL, p ⫽ 0.004). Measurements of the E/A ratio showed no correlation with NT-proBNP levels ( ⫽ 0.25, p ⫽ 0.19; Fig 7).
Table 2. N-Terminal Probrain Natriuretic Peptide and Clinical Characteristics Among Patients Undergoing Elective Cardiac Surgery Divided by an E/E= Ratio Above and Below 15
NT-proBNP (pg/mL)* Age (y) BMI (kg/m2) EF (%) Atrial fibrillation (n) Sex ⫽ male (%) CABG (n) AVR (n) CABG ⫹ AVR (n) EuroSCORE
E/E= ⱕ15
E/E= ⬎15
33 (12-54) 70 (67-72) 26 (25-27) 52 (46-58) 1 77 8 3 2 4.8 (3.6-6.0)
113 (52-174) 72 (70-75) 27 (25-29) 49 (43-55) 1 44 3 8 5 5.4 (4.6-6.2)
Abbreviations: AVR, aortic valve replacement; BMI, body mass index; CABG, coronary artery bypass grafting; EF, ejection fraction; NT-proBNP, N-terminal probrain natriuretic peptide. *Significant differences.
This study showed that advanced echocardiographic measurements of systolic and diastolic function correlated with NT-proBNP levels. Strain measurements from the left ventricle have been shown to correlate with neurohormonal levels.23,24 This study confirmed this finding, thus improving the position of strain measurements as an indicator of global LV function. The method has potential as an easily performed bedside tool with minimal user dependence. Although STU is easy to use and independent of the insonating angle, it has limitations. These limitations have been examined in previous studies and focused on the need for high frame rate and image quality.9 The authors also found good agreement between the Doppler-derived E/E= measurements and NT-proBNP levels, but E/A failed to show any relation with NT-proBNP. The E/E= and E/A ratios have been studied as markers of diastolic dysfunction, but E/E= is recognized primarily as an important marker of diastolic dysfunction.1,25 However, although the Doppler methods are very applicable, they have limitations. Doppler methods depend on the insonating angle, require technical skills to perform, and the E/A ratio is influenced by pseudonormalization. The plasma level of NT-proBNP has been studied extensively and is recognized as a reliable marker of cardiac dysfunction,11,12 However, NT-proBNP cannot distinguish systolic from diastolic heart failure. When diagnosing diastolic heart failure NT-proBNP plays an important role, but only in combination with echocardiography.1 Problems with the interpretation of NT-proBNP also arise in patients with kidney failure and lung disease.26 In summary, NT-proBNP measurements yield substantial information in the perioperative setting and STU combined with Doppler measurements add to this information by discriminating between systolic and diastolic failure. Measurements of global strain achieved by combining results from the 3 standard apical imaging planes were
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FREDERIKSEN ET AL
Fig. 2. Scatter plot showing the preoperative relation between global strain data from all 3 apical views achieved by speckle tracking ultrasound measurements and plasma levels of N-terminal probrain natriuretic peptide (NT-proBNP).
interchangeable with strain from only the apical 4-chamber view. The use of only 1 acoustic window makes it very simple to implement STU in existing point-of-care ultrasound protocols based on simple 2-dimensional imaging.5,27
Fig. 3. Scatter plot showing the preoperative relation between apical 4-chamber strain data from the speckle tracking ultrasound measurements and plasma levels of Nterminal probrain natriuretic peptide (NT-proBNP).
However, caution should be exercised when using only 1 imaging plane to calculate strain, because severe regional myocardial dyskinesia not visualized in the plane used could hamper the results.
ECHOCARDIOGRAPHIC SYSTOLIC AND DIASTOLIC FUNCTION
201
Fig. 4. Scatter plot showing the preoperative relation between apical 4-chamber strain and global strain data from the speckle tracking ultrasound measurements. The solid line represents the line of identity.
Study Limitations This study focused only on NT-proBNP and not BNP, because recent studies have shown the two to be comparable.28 It is well known that NT-proBNP is influenced by age and sex; a larger study population thus would have allowed an evaluation of this influence according to previously published studies. In addition, this study described only the
association between NT-proBNP and echocardiographic indices but did not yield any prognostic information that could further substantiate the use of echocardiography in the preoperative setting. The study was conducted in patients undergoing aortic valve replacement and coronary artery bypass grafting and covered a large variety of patients with heart conditions, but
Fig. 5. Difference in mean plot showing speckle tracking ultrasound global strain versus apical 4-chamber view data. Limits of agreement (2 standard deviations) are shown as dotted lines.
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Fig. 6. Scatter plot showing preoperative E/E= data from the tissue Doppler and pulsed-wave Doppler measurements in relation to plasma levels of N-terminal probrain natriuretic peptide (NT-proBNP).
it is not possible to extrapolate the results to other patient categories. CONCLUSIONS
A correlation was found between plasma levels of NTproBNP and STU strain measurements by an easily employed
Fig. 7. Scatter plot showing preoperative E/A data from the mitral inflow profile in relation to the plasma levels of N-terminal probrain natriuretic peptide (NT-proBNP).
method applicable in the anesthesia and preoperative settings. In addition, the well-established marker of diastolic function, E/E=, correlated well with NT-proBNP, whereas the E/A ratio failed to show any association. Further randomized studies may focus on different outcomes, including morbidity and mortality, when collecting data on cardiovascular function in the anesthesia and preoperative settings.
ECHOCARDIOGRAPHIC SYSTOLIC AND DIASTOLIC FUNCTION
203
REFERENCES 1. Paulus WJ, Tschöpe C, Sanderson JE, et al: How to diagnose diastolic heart failure: A consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur Heart J 28:2539-2550, 2007 2. Owan TE, Redfield MM: Epidemiology of diastolic heart failure. Prog Cardiovasc Dis 47:320-332, 2005 3. Reich DL, Bodian CA, Krol M, et al: Intraoperative hemodynamic predictors of mortality, stroke, and myocardial infarction after coronary artery bypass surgery. Anesth Analg 89:814-822, 1999 4. Reich DL, Bennett-Guerrero E, Bodian CA, et al: Intraoperative tachycardia and hypertension are independently associated with adverse outcome in noncardiac surgery of long duration. Anesth Analg 95:273-277, 2002 5. Jensen MB, Sloth E, Larsen KM, et al: Transthoracic echocardiography for cardiopulmonary monitoring in intensive care. Eur J Anaesthesiol 21:700-707, 2004 6. Sutherland GR, Di Salvo G, Claus P, et al: Strain and strain rate imaging: A new clinical approach to quantifying regional myocardial function. J Am Soc Echocardiogr 17:788-802, 2004 7. Heimdal A, Støylen A, Torp H, et al: Real-time strain rate imaging of the left ventricle by ultrasound. J Am Soc Echocardiogr 11:1013-1019, 1998 8. Ingul CB, Torp H, Aase SA, et al: Automated analysis of strain rate and strain: Feasibility and clinical implications. J Am Soc Echocardiogr 18:411-418, 2005 9. Sivesgaard K, Christensen SD, Nygaard H, et al: Speckle tracking ultrasound is independent of insonation angle and gain: An in vitro investigation of agreement with sonomicrometry. J Am Soc Echocardiogr 22:852-858, 2009 10. Kroijer R, Eldrup N, Paaske WP, et al: Left ventricular longitudinal strain for perioperative cardiac monitoring in aortic aneurysm surgery using transthoracic 2-dimensional echocardiography: A feasibility and repeatability study. J Cardiothorac Vasc Anesth 24:37-42, 2010 11. Krishnaswamy P, Lubien E, Clopton P, et al: Utility of B-natriuretic peptide levels in identifying patients with left ventricular systolic or diastolic dysfunction. Am J Med 111:274-279, 2001 12. de Lemos JA, McGuire DK, Drazner MH: B-type natriuretic peptide in cardiovascular disease. Lancet 362:316-322, 2003 13. Januzzi JL, van Kimmenade R, Lainchbury J, et al: NT-proBNP testing for diagnosis and short-term prognosis in acute destabilized heart failure: An international pooled analysis of 1256 patients: The International Collaborative of NT-proBNP Study. Eur Heart J 27:330337, 2006 14. Cerrahoglu M, Iskesen I, Tekin C, et al: N-terminal ProBNP levels can predict cardiac failure after cardiac surgery. Circ J 71:79-83, 2007 15. Ryding AD, Kumar S, Worthington AM, et al: Prognostic value of brain natriuretic peptide in noncardiac surgery: A meta-analysis. Anesthesiology 111:311-319, 2009
16. Dalen H, Thorstensen A, Aase SA, et al: Segmental and global longitudinal strain and strain rate based on echocardiography of 1266 healthy individuals: The HUNT study in Norway. Eur J Echocardiogr 11:176-183, 2010 17. Ommen SR, Nishimura RA, Appleton CP, et al: Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: A comparative simultaneous Doppler-catheterization study. Circulation 102:1788-1794, 2000 18. Hillis GS, Moller JE, Pellikka PA, et al: Noninvasive estimation of left ventricular filling pressure by E/E= is a powerful predictor of survival after acute myocardial infarction. J Am Coll Cardiol 43:360367, 2004 19. Nagueh SF, Appleton CP, Gillebert TC, et al: Recommendations for the evaluation of left ventricular diastolic function by echocardiography. Eur J Echocardiogr 10:165-193, 2009 20. Kasner M, Westermann D, Steendijk P, et al: Utility of Doppler echocardiography and tissue Doppler imaging in the estimation of diastolic function in heart failure with normal ejection fraction: A comparative Doppler-conductance catheterization study. Circulation 116:637-647, 2007 21. Bland JM, Altman DG: Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1:307-310, 1986 22. Bland JM, Altman DG: Measuring agreement in method comparison studies. Stat Methods Med Res 8:135-160, 1999 23. Yoneyama A, Koyama J, Tomita T, et al: Relationship of plasma brain-type natriuretic peptide levels to left ventricular longitudinal function in patients with congestive heart failure assessed by strain Doppler imaging. Int J Cardiol 130:56-63, 2008 24. Knebel F, Eddicks S, Schimke I, et al: Myocardial tissue Doppler echocardiography and N-terminal B-type natriuretic peptide (NTproBNP) in diastolic and systolic heart failure. Cardiovasc Ultrasound 6:45, 2008 25. Ceyhan C, Unal S, Yenisey C, et al: The role of N terminal pro-brain natriuretic peptide in the evaluation of left ventricular diastolic dysfunction: Correlation with echocardiographic indexes in hypertensive patients. Int J Cardiovasc Imaging 24:253-259, 2008 26. Galasko GI, Lahiri A, Barnes SC, et al: What is the normal range for N-terminal pro-brain natriuretic peptide? How well does this normal range screen for cardiovascular disease? Eur Heart J 26:2269-2276, 2005 27. Jakobsen CJ, Torp P, Sloth E: Perioperative feasibility of imaging the heart and pleura in patients with aortic stenosis undergoing aortic valve replacement. Eur J Anaesthesiol 24:589-595, 2007 28. Park HJ, Baek SH, Jang SW, et al: Direct comparison of B-type natriuretic peptide and N-terminal pro-BNP for assessment of cardiac function in a large population of symptomatic patients. Int J Cardiol 140:336-343, 2010
tracking ultrasound measurement and NT-proBNP levels was ⴝ 0.35 (p ⴝ 0.026). With a cutoff value of ⴚ15% in global strain measurements, there was a significant difference in NT-proBNP levels (117 v 57 pg/mL, p ⴝ 0.048). E/E= values correlated with NT-proBNP levels ( ⴝ 0.46, p ⴝ 0.011). With a cutoff of 15 in E/E= values, there were significant differences in corresponding NT-proBNP levels (33 v 113 pg/mL, p ⴝ 0.004). Conclusions: A correlation was found between plasma levels of NT-proBNP and speckle tracking ultrasound strain measurements by an easily employed method applicable in the anesthesia and preoperative settings. In addition, the well-established marker of diastolic function, E/E=, correlated well with NT-proBNP, whereas the E/A ratio failed to show any association. © 2012 Elsevier Inc. All rights reserved.
T
of this study was to evaluate cardiac function by ultrasound imaging in combination with NT-proBNP before cardiac surgery. A secondary aim was to evaluate a simplified assessment of STU in the preoperative period using a single imaging plane and to assess its feasibility by comparison with a composite value from 3 imaging planes.
HE PREVALENCE OF systolic and diastolic heart failure is high and the prognosis is poor.1,2 Clinicians need information on hemodynamic performance and cardiovascular status in patients with a failing heart during cardiac and noncardiac surgery.3,4 Echocardiography is noninvasive and provides specific information about systolic and diastolic function, including important cardiac pathology.5 Systolic function can be assessed by measuring the degree of deformation in the myocardium by speckle tracking ultrasound (STU) strain measurements.6,7 A deformation analysis can be performed semiautomatically on 2-dimensional images acquired during conventional transthoracic echocardiography.8-10 Thus, physicians with limited training in echocardiography can generate measurements of myocardial deformation with a high degree of observer independency.10 Left ventricular (LV) diastolic function includes relaxation and filling of the chamber and advanced Doppler methods measuring blood flow velocities and tissue velocities are recommended for quantification.1 Overall assessment of cardiac function can be achieved by measuring serum N-terminal probrain natriuretic peptide (NTproBNP). Several studies have shown plasma levels of NTproBNP to be elevated in patients with systolic and diastolic heart failure11,12 and correlated to the prognosis in systolic heart failure.13 Similarly, studies have evaluated the use of NTproBNP levels as a prognostic tool during the perioperative period.14,15 The combination of cardiac biomarkers and ultrasound imaging may increase preoperative information on cardiac function, leading to increased safety during anesthesia and surgery. The authors hypothesized that preoperative NT-proBNP correlates well with longitudinal strain measurements and with Doppler measurements of diastolic function. The primary aim
KEY WORDS: echocardiography, preoperative, cardiac anesthesia, cardiac function, speckle tracking ultrasound, Doppler, strain, N-terminal probrain natriuretic peptide
METHODS Patients undergoing aortic valve replacement and/or coronary artery bypass grafting were included in the study that was performed in accordance with the Declaration of Helsinki and approved by the regional ethics committee (no M-ÅA-20050038). Written informed consent was obtained from all patients. Blood sampling and ultrasound examination were carried out the day before surgery. Plasma NT-proBNP concentration was determined with a commercially available kit (Roche Diagnostics, Mannheim, Germany). A Vivid E9 (GE Healthcare, Horten, Norway) ultrasound system equipped with an M5S-D phased array transducer (1.5 to 4.5 MHz) with second harmonic imaging was used for data acquisition. Examinations were performed with the patient in the left lateral position by a technician experienced in echocardiography. The protocol included imaging of the apical 4- and 2-chamber and long-axis views and the
From the *Department of Anesthesiology and Intensive Care, Aarhus University Hospital, and the †Institute of Clinical Medicine, Faculty of Health Sciences, Aarhus University, Skejby, Denmark. This work was funded by the John and Birthe Meyer Foundation. Address reprint requests to Christian Alcaraz Frederiksen, MD, Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Skejby, Brendstrupgaardsvej 100, DK-8200 Aarhus N, Denmark. E-mail: [email protected] © 2012 Elsevier Inc. All rights reserved. 1053-0770/2602-0004$36.00/0 doi:10.1053/j.jvca.2011.07.022
Journal of Cardiothoracic and Vascular Anesthesia, Vol 26, No 2 (April), 2012: pp 197-203
197
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Fig. 1. The 3 standard apical imaging planes and the corresponding bull’s eye plot. (Upper left) Apical 4-chamber view. (Upper right) Apical 2-chamber view. (Lower left) Apical long-axis view. (Lower right) Bull’s eye plot of the left ventricle showing myocardial strain in all segments. Strain data are based on calculations of measurements from all 3 apical imaging planes.
parasternal long- and short-axis views. Raw data were stored digitally in cineloop format defined by the R wave on the corresponding electrocardiogram for off-line analyses using EchoPac software (GE Healthcare). LV ejection fraction was calculated using the Simpson biplane method and LV deformation was assessed by STU based on the 3 standard imaging planes in the apical window. The method relies on natural acoustic markers in the tissue and is expressed as a percentage of change in tissue length during the cardiac cycle as the myocardial tissue shortens during contraction; longitudinal strain is expressed as negative values. The software processing is semiautomatic and based on manually placed regions of interest, including timing of the end of diastole and aortic valve closure. Deformation can be expressed as strain from a single imaging plane or as global strain calculated as the average value from the 3 apical imaging planes (Fig 1). Longitudinal, radial, or torsion strain measurements can be performed. All strain measurements in the present study were calculated as longitudinal strain. The cutoff value for STU strain measurements was ⫺15% in accordance with the age of the study population.16 Pulsed-wave Doppler was used for measuring mitral inflow blood velocities. The first peak in blood velocity early in diastole is designated E and the late or atrial peak in blood flow velocity is designated A. Tissue Doppler imaging of the septal mitral annulus was used for measuring tissue velocities throughout the cardiac cycle, with E= and A= corresponding to the above-mentioned mitral
inflow velocities. Two ratios related to LV diastolic function were calculated. The E/A ratio characterizes the filling pattern of the left ventricle. The E/E= ratio takes not only the blood flow but also the tissue movement into consideration and is related closely to LV filling pressures. Cutoff ratios between normal and abnormal values were 15 for E/E= and 0.9 for E/A.17-20 Comparisons of NT-proBNP and strain/Doppler values were based on the Spearman correlation and comparisons of NT-proBNP above and below the cutoff values were based on the Wilcoxon rank-sum test. STU data were compared according to the analyses of Bland and Altman.21,22 The level of statistical significance was p ⬍ 0.05. Tests and calculations were carried out using Stata 11.0 (StataCorp LP, College Station, TX). RESULTS
Forty patients were enrolled into the study. Basic clinical data and data on LV ejection fraction are presented in Tables 1, 2, and 3. Because of technical problems, E/E= and E/A measurements were available in only 29 subjects. No patient had a serum creatinine level ⬎200 mol/L preoperatively. A decrease in myocardial longitudinal strain correlated with an elevation in NT-proBNP levels. This applied when using global longitudinal strain data from all 3 imaging planes ( ⫽ 0.35, p ⫽ 0.026; Fig 2) and when using only STU data from the
ECHOCARDIOGRAPHIC SYSTOLIC AND DIASTOLIC FUNCTION
Table 1. N-Terminal Probrain Natriuretic Peptide and Clinical Characteristics Among Patients Undergoing Elective Cardiac Surgery Divided by Strain Above and Below ⴚ15%
NT-proBNP (pg/mL)* Age (y) BMI (kg/m2)* EF (%) Atrial fibrillation (n) Sex ⫽ male (%) CABG (n) AVR (n) CABG ⫹ AVR (n) EuroSCORE
STU Strain ⬎⫺15%
STU Strain ⱕ⫺15%
117 (66-168) 70 (68-73) 28 (27-30) 48 (42-55) 0 70 8 5 7 5.2 (4.2-6.1)
57 (32-81) 72 (70-74) 25 (23-26) 51 (47-56) 2 50 5 11 4 5.5 (4.7-6.3)
Abbreviations: AVR, aortic valve replacement; BMI, body mass index; CABG, coronary artery bypass grafting; EF, ejection fraction; NT-proBNP, N-terminal probrain natriuretic peptide; STU, speckle tracking ultrasound. *Significant differences.
199
Table 3. N-Terminal Probrain Natriuretic Peptide and Clinical Characteristics Among Patients Undergoing Elective Cardiac Surgery Divided by an E/A Ratio Above and Below 0.9
NT-proBNP (pg/mL) Age (y) BMI (kg/m2) EF (%) Atrial fibrillation (n) Sex ⫽ male (%) CABG (n) AVR (n) CABG ⫹ AVR (n) EuroSCORE
E/A ⱕ0.9
E/A ⬎0.9
89 (32-146) 70 (68-73) 27 (25-29) 52 (45-58) 0 55 5 4 2 5.3 (4.2-6.3)
70 (19-122) 72 (69-74) 26 (24-28) 50 (44-56) 2 61 6 7 5 5.0 (4.1-5.9)
Abbreviations: AVR, aortic valve replacement; BMI, body mass index; CABG, coronary artery bypass grafting; EF, ejection fraction; NT-proBNP, N-terminal probrain natriuretic peptide.
DISCUSSION
apical 4-chamber view ( ⫽ 0.43, p ⫽ 0.007; Fig 3). Furthermore, applying a cutoff value of ⫺15% to global strain measurements yielded a significant difference in NT-proBNP levels between patients with low (117 pg/mL) and high (57 pg/mL) global strain (p ⫽ 0.048). Global longitudinal strain and longitudinal strain from the apical 4-chamber view were compared using Bland-Altman analysis and showed a good agreement (p ⫽ 0.34; Figs 4 and 5). A decrease in diastolic function measured by an increase in E/E= correlated with an elevation in NT-proBNP levels ( ⫽ 0.46, p ⫽ 0.011; Fig 6). When a cutoff value of 15 was applied to E/E= values, there was a significant difference in corresponding NT-proBNP levels (33 v 113 pg/mL, p ⫽ 0.004). Measurements of the E/A ratio showed no correlation with NT-proBNP levels ( ⫽ 0.25, p ⫽ 0.19; Fig 7).
Table 2. N-Terminal Probrain Natriuretic Peptide and Clinical Characteristics Among Patients Undergoing Elective Cardiac Surgery Divided by an E/E= Ratio Above and Below 15
NT-proBNP (pg/mL)* Age (y) BMI (kg/m2) EF (%) Atrial fibrillation (n) Sex ⫽ male (%) CABG (n) AVR (n) CABG ⫹ AVR (n) EuroSCORE
E/E= ⱕ15
E/E= ⬎15
33 (12-54) 70 (67-72) 26 (25-27) 52 (46-58) 1 77 8 3 2 4.8 (3.6-6.0)
113 (52-174) 72 (70-75) 27 (25-29) 49 (43-55) 1 44 3 8 5 5.4 (4.6-6.2)
Abbreviations: AVR, aortic valve replacement; BMI, body mass index; CABG, coronary artery bypass grafting; EF, ejection fraction; NT-proBNP, N-terminal probrain natriuretic peptide. *Significant differences.
This study showed that advanced echocardiographic measurements of systolic and diastolic function correlated with NT-proBNP levels. Strain measurements from the left ventricle have been shown to correlate with neurohormonal levels.23,24 This study confirmed this finding, thus improving the position of strain measurements as an indicator of global LV function. The method has potential as an easily performed bedside tool with minimal user dependence. Although STU is easy to use and independent of the insonating angle, it has limitations. These limitations have been examined in previous studies and focused on the need for high frame rate and image quality.9 The authors also found good agreement between the Doppler-derived E/E= measurements and NT-proBNP levels, but E/A failed to show any relation with NT-proBNP. The E/E= and E/A ratios have been studied as markers of diastolic dysfunction, but E/E= is recognized primarily as an important marker of diastolic dysfunction.1,25 However, although the Doppler methods are very applicable, they have limitations. Doppler methods depend on the insonating angle, require technical skills to perform, and the E/A ratio is influenced by pseudonormalization. The plasma level of NT-proBNP has been studied extensively and is recognized as a reliable marker of cardiac dysfunction,11,12 However, NT-proBNP cannot distinguish systolic from diastolic heart failure. When diagnosing diastolic heart failure NT-proBNP plays an important role, but only in combination with echocardiography.1 Problems with the interpretation of NT-proBNP also arise in patients with kidney failure and lung disease.26 In summary, NT-proBNP measurements yield substantial information in the perioperative setting and STU combined with Doppler measurements add to this information by discriminating between systolic and diastolic failure. Measurements of global strain achieved by combining results from the 3 standard apical imaging planes were
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Fig. 2. Scatter plot showing the preoperative relation between global strain data from all 3 apical views achieved by speckle tracking ultrasound measurements and plasma levels of N-terminal probrain natriuretic peptide (NT-proBNP).
interchangeable with strain from only the apical 4-chamber view. The use of only 1 acoustic window makes it very simple to implement STU in existing point-of-care ultrasound protocols based on simple 2-dimensional imaging.5,27
Fig. 3. Scatter plot showing the preoperative relation between apical 4-chamber strain data from the speckle tracking ultrasound measurements and plasma levels of Nterminal probrain natriuretic peptide (NT-proBNP).
However, caution should be exercised when using only 1 imaging plane to calculate strain, because severe regional myocardial dyskinesia not visualized in the plane used could hamper the results.
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Fig. 4. Scatter plot showing the preoperative relation between apical 4-chamber strain and global strain data from the speckle tracking ultrasound measurements. The solid line represents the line of identity.
Study Limitations This study focused only on NT-proBNP and not BNP, because recent studies have shown the two to be comparable.28 It is well known that NT-proBNP is influenced by age and sex; a larger study population thus would have allowed an evaluation of this influence according to previously published studies. In addition, this study described only the
association between NT-proBNP and echocardiographic indices but did not yield any prognostic information that could further substantiate the use of echocardiography in the preoperative setting. The study was conducted in patients undergoing aortic valve replacement and coronary artery bypass grafting and covered a large variety of patients with heart conditions, but
Fig. 5. Difference in mean plot showing speckle tracking ultrasound global strain versus apical 4-chamber view data. Limits of agreement (2 standard deviations) are shown as dotted lines.
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Fig. 6. Scatter plot showing preoperative E/E= data from the tissue Doppler and pulsed-wave Doppler measurements in relation to plasma levels of N-terminal probrain natriuretic peptide (NT-proBNP).
it is not possible to extrapolate the results to other patient categories. CONCLUSIONS
A correlation was found between plasma levels of NTproBNP and STU strain measurements by an easily employed
Fig. 7. Scatter plot showing preoperative E/A data from the mitral inflow profile in relation to the plasma levels of N-terminal probrain natriuretic peptide (NT-proBNP).
method applicable in the anesthesia and preoperative settings. In addition, the well-established marker of diastolic function, E/E=, correlated well with NT-proBNP, whereas the E/A ratio failed to show any association. Further randomized studies may focus on different outcomes, including morbidity and mortality, when collecting data on cardiovascular function in the anesthesia and preoperative settings.
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